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Narifumi Akaza,1 Kazuto Takasaki,2 Eri Nishiyama,2 Atsuko Usui,2 Shiori Miura,1 Aya Yokoi,3,4 Kyoko Futamura,4 Kayoko Suzuki,4 Youichi Yashiro,1 Akiko Yagami4 1Research Laboratories, Nippon Menard Cosmetic Co., Ltd., Nagoya, Japan; 2Fasmac Co., Ltd., Kanagawa, Japan; 3Nihombashi Irodori Dermatology Clinic, Tokyo, Japan; 4Department of Allergology, Fujita Health University School of Medicine, Nagoya, JapanCorrespondence: Narifumi Akaza, Research Laboratories, Nippon Menard Cosmetic Co., Ltd., 2-7 Torimi-cho, Nishi-ku, Nagoya, Aichi, 451-0071, Japan, Tel +81 52 531 6263, Fax +81 52 531 6277, Email akaza.narifumi@menard.co.jpBackground: Acne vulgaris (acne) and cutaneous resident microorganisms are considered to be closely related. However, the bacterial and fungal microbiota in the comedonal contents of inflammatory acne lesions have not yet been investigated in detail.Purpose: To clarify the relationship between cutaneous microorganisms and acne, we examined the microbiome in the comedonal contents of inflammatory acne and on the facial skin of patients with acne using 16s rRNA and ITS gene sequencing with a next-generation sequencer (NGS).Patients and Methods: Twenty-two untreated Japanese acne outpatients were examined. The comedonal contents of inflammatory acne lesions on the face were collected using a comedo extractor. Skin surface samples from facial skin were collected using the swab method.Results: The results obtained revealed that the predominant bacteria in the comedonal contents of inflammatory acne were Cutibacterium spp. (more prominent in areas with large amounts of sebum), while those on the skin surface were Staphylococcus spp. Malassezia spp., particularly Malassezia restricta, were the predominant fungi in both the comedonal contents of inflammatory acne and on the skin surface. The bacterial microbiome in comedonal contents exhibited stronger metabolic activity, including the production of enzymes related to acne, than that on the skin surface.Conclusion: These results indicate that acne is an inflammatory disease involving the overgrowth of Cutibacterium acnes and other cutaneous resident microorganisms, including Malassezia spp.Keywords: acne vulgaris, Cutibacterium, Staphylococcus, Malassezia, microbiome, microbiota, next generation sequencing

Daiji Nagayama,1,2 Kentaro Fujishiro,3 Kenji Suzuki,3 Kohji Shirai4 1Department of Internal Medicine, Nagayama Clinic, Tochigi, Japan; 2Center of Diabetes, Endocrinology and Metabolism, Toho University, Sakura Medical Center, Chiba, Japan; 3Research and Development Division, Japan Health Promotion Foundation, Tokyo, Japan; 4Internal Medicine, Mihama Hospital, Chiba, JapanCorrespondence: Daiji Nagayama, Nagayama Clinic, 2-12-22, Tenjin-Cho, Oyama-City, Tochigi, 323-0032, Japan, Tel +81-285-22-0219, Fax +81-285-22-0219, Email deverlast96071@gmail.comAbstract: Cardio-ankle vascular index (CAVI) was developed to reflect the stiffness of the arterial tree from the aortic origin to the ankle. This arterial stiffness parameter is useful for assessing the severity of cardiovascular disease (CVD) and its risk. However, compared to pulse wave velocity (PWV), the conventional gold standard of arterial stiffness parameter, there has been a concern regarding CAVI that there are fewer longitudinal studies for CVD. Furthermore, the accuracy of CAVI for atherosclerotic diseases compared to other parameters has not been well validated. This review article aims to summarize recent findings to clarify the predictive ability of CAVI in longitudinal studies. First, several large longitudinal studies have found that not only baseline CAVI but also CAVI changes during the observation period predict cardiovascular events. Second, CAVI may have superior discriminatory power for all-cause mortality and major adverse cardiovascular endpoints compared to PWV. Furthermore, one large longitudinal study found CAVI to be a stronger predictor for renal function decline compared to PWV as well as CAVI0, a variant of CAVI that mathematically excludes BP dependence. Additionally, CAVI shows the properties that allow the elucidation of specific hemodynamics in aortic valve disease or hypovolemia. In conclusion, CAVI may be a modifiable arterial stiffness parameter not only for predicting and preventing atherosclerotic diseases but also for elucidating specific hemodynamic pathophysiology.Keywords: cardio-ankle vascular index, pulse wave velocity, CAVI0, longitudinal study, cardiovascular disease, renal function decline

Keisuke Suzuki, Shiho Suzuki, Tomohiko Shiina, Saro Kobayashi, Koichi Hirata Department of Neurology, Dokkyo Medical University, Mibu, JapanCorrespondence: Keisuke Suzuki, Department of Neurology, Dokkyo Medical University, 880 Kitakobayashi, Shimotsuga, Mibu, Tochigi, 321-0293, Japan, Tel +81-282-86-1111, Fax +81-282-86-5884, Email keisuke@dokkyomed.ac.jpAbstract: Central sensitization (CS) is an increase in the responsiveness of nociceptive neurons in the central nervous system to their normal afferent input. As a result, even minor irritation can induce severe pain, leading to the chronicity and severity of various diseases, such as neurological disorders. CS is associated with migraine, which is a major neurological disorder that inflicts a high disability in daily life. Specifically, CS is thought to be involved in the pathogenesis of cutaneous allodynia as well as chronification of migraine. In this article, we reviewed the association between CS and migraine, including pathophysiological aspects and evidence from clinical studies. We suggest that appropriate screening and management of CS in migraine could further improve the quality of life of migraine patients.Keywords: migraine, central sensitization, cutaneous allodynia, restless legs syndrome

Keita Suzuki,1 Hiromasa Tsujiguchi,1– 3 Akinori Hara,1– 3 Oanh Kim Pham,1 Sakae Miyagi,3,4 Thao Thi Thu Nguyen,5 Haruki Nakamura,1 Fumihiko Suzuki,2,6 Tomoko Kasahara,2 Yukari Shimizu,7 Yohei Yamada,2 Yasuhiro Kambayashi,8 Hirohito Tsuboi,9 Takehiro Sato,3,10 Takayuki Kannon,3,10 Kazuyoshi Hosomichi,3,10 Atsushi Tajima,3,10 Toshinari Takamura,11 Hiroyuki Nakamura1– 3 1Department of Hygiene and Public Health, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan; 2Department of Public Health, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan; 3Kanazawa University Advanced Preventive Medical Sciences Research Center, Kanazawa, Ishikawa, Japan; 4Innovative Clinical Research Center, Kanazawa University, Kanazawa, Ishikawa, Japan; 5Department of Epidemiology, Faculty of Public Health, Haiphong University of Medicine and Pharmacy, Hai Phong, Vietnam; 6Community Medicine Support Dentistry, Ohu University Hospital, Koriyama, Fukushima, Japan; 7Department of Nursing, Faculty of Health Sciences, Komatsu University, Komatsu, Ishikawa, Japan; 8Department of Public Health, Faculty of Veterinary Medicine, Okayama University of Science, Imabari, Ehime, Japan; 9Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan; 10Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan; 11Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, JapanCorrespondence: Keita Suzuki, Department of Hygiene and Public Health, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 13-1, Takara-machi, Kanazawa, Ishikawa, 920-8640, Japan, Tel +81 76 265 2218, Fax +81 76 234 4233, Email ksuzuk@staff.kanazawa-u.ac.jpBackground: Previous studies examined the association between chronic pain (CP) and serum 25-hydroxyvitamin D (25(OH)D) concentrations; however, the findings obtained were inconsistent. Single nucleotide polymorphisms (SNP) associated with the transcriptional activity of the vitamin D receptor (VDR) gene may influence the association of 25(OH)D levels with CP. We aimed to clarify the association between CP, serum 25(OH)D concentration, and SNPs.Methods: In the Shika study, we performed a cross-sectional analysis of 551 participants older than 40 years who were asked whether they had been having persistent pain lasting for at least 3 months in any part of the body on a self-administered questionnaire. Serum 25(OH)D concentrations were assessed as a biomarker of the vitamin D status using a radioimmunoassay. rs731236, rs7975232, rs1544410, rs2228570, and rs11568820 were identified using peripheral blood samples, and participants were assigned to those with or without the minor allele for each SNP.Results: The prevalence of CP was 37.2%. We observed a tendency for lower 25(OH)D levels in participants with CP than in those without CP in the hetero/minor group of rs11568820, which is a polymorphism within the CDX2-binding site in the 1e promoter region of the VDR gene. Furthermore, a logistic regression analysis revealed that lower serum 25(OH)D concentrations were significantly associated with CP in the hetero/minor group, but not in the major group.Conclusion: These results suggest that sufficient serum 25(OH)D concentration reduces the risk of CP in individuals with the minor allele of the CDX2 polymorphism.Keywords: chronic pain, 25-hydroxyvitamin D, vitamin D receptor gene, promoter, polymorphism, epidemiology

Daiji Nagayama,1,2 Kentaro Fujishiro,3 Keijiro Nakamura,4 Yasuhiro Watanabe,2 Takashi Yamaguchi,2 Kenji Suzuki,3 Kazuhiro Shimizu,5 Atsuhito Saiki,2 Kohji Shirai6 1Department of Internal Medicine, Nagayama Clinic, Tochigi, Japan; 2Center of Diabetes, Endocrinology and Metabolism, Toho University, Sakura Medical Center, Chiba, Japan; 3Japan Health Promotion Foundation, Tokyo, Japan; 4Division of Cardiovascular Medicine, Toho University, Ohashi Medical Center, Tokyo, Japan; 5Division of Cardiovascular Medicine, Toho University, Sakura Medical Center, Chiba, Japan; 6Department of Internal Medicine, Mihama Hospital, Chiba, JapanCorrespondence: Daiji NagayamaNagayama Clinic, 2-12-22, Tenjin-Cho, Oyama-City, Tochigi, 323-0032, Japan, Tel/Fax +81-285-22-0219, Email deverlast96071@gmail.comAim: Physiological tests to assess systemic vascular function are not included in the risk score for atrial fibrillation (AF). We aimed to examine whether cardio-ankle vascular index (CAVI), a systemic arterial stiffness parameter, is associated with the presence of AF in Japanese general population.Methods: A cross-sectional study (N = 47,687) and a cohort study (N = 5418, four consecutive years) in Japanese urban residents who participated in annual health screening were conducted.Results: A total of 164 subjects (0.34%) had AF in the cross-sectional data. After propensity score matching for age and gender, logistic regression analysis revealed that CAVI is independently associated with AF, as are body mass index and estimated glomerular filtration rate. In a 4-year cohort study, 22 subjects (0.41%) with new-appearance of AF showed higher CAVI at baseline than those without. In the receiver-operating-characteristic curve analysis, the area under the curve, which is a measure of predictability, of CAVI for the new-appearance of AF was 0.747, and the cut-off value of CAVI was 8.0. Kaplan–Meier analysis revealed that the cumulative incidence of new-appearance of AF was higher in subjects with CAVI ≥ 8.0 compared to those with CAVI < 8.0. In Cox-proportional hazards analysis, CAVI ≥ 8.0 as well as gender were identified as independent predictors for the new-appearance of AF, whereas age ≥ 65 years was not.Conclusion: Increased CAVI may represent a major modifiable risk factor for the development of AF. Studies are needed to confirm that CAVI is a predictor of AF independent of various AF risk factors and that CAVI-lowering interventions can prevent new-appearance or recurrence of AF.Keywords: atrial fibrillation, cardio-ankle vascular index, CAVI, arterial stiffness, health screening

Teppei Hagino,1,2 Shizuka Okazaki,1 Naotaka Serizawa,1 Kaori Suzuki,1 Mio Kaga,2 Yohei Otsuka,2 Erina Mikami,2 Toshihiko Hoashi,2 Hidehisa Saeki,2 Hiroki Matsuda,3 Hiroshi Mitsui,3 Naoko Kanda1 1Department of Dermatology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan; 2Department of Dermatology, Nippon Medical School, Tokyo, Japan; 3Department of Dermatology, Tokyo Teishin Hospital, Tokyo, JapanCorrespondence: Naoko KandaDepartment of Dermatology, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamagari, Inzai, Chiba, 270-1694 JapanTel +81 476 99 1111Fax +81 476 99 1909Email n-kanda@nms.ac.jpPurpose: Alopecia areata (AA) is characterized by non-scarring, patchy hair loss caused by autoimmune reactions to anagen hair follicles. The pathogenesis of AA may be affected by the diet. However, the dietary habits of patients with AA have not been precisely examined. Therefore, the aim of this study was to investigate the dietary habits of patients with AA in comparison to those of healthy controls.Patients and Methods: We evaluated the dietary habits of 70 adult Japanese patients with AA using a brief-type self-administered diet history questionnaire and compared them to the habits of age- and sex-matched healthy controls.Results: Japanese patients with AA had a higher body mass index (BMI) and higher intakes of vitamin C and fruit than the controls. Logistic regression analysis showed that AA was associated with BMI. Retinol intake was positively correlated with severity of alopecia tool (SALT) score, and linear regression analysis revealed that retinol intake was a predictor of SALT score. Retinol intake among patients with moderate to severe AA (ie, a SALT score > 25) was higher than that in patients with mild AA (a SALT score ≤ 25). The mean age of AA patients with atopic dermatitis (AD) was lower than that of AA patients without AD; however, there were no differences in nutrient or food intake between these two groups. Logistic regression analysis showed that the comorbidity AD was negatively associated with age.Conclusion: AA was associated with a high BMI, and high retinol intake was a predictor of SALT score. Further studies should be conducted to clarify whether dietary intervention to reduce BMI or limit retinol intake can alter the development or severity of AA.Keywords: retinol, vitamin C, body mass index, atopic dermatitis

Yasushi Kawamata,1 Norio Sugawara,1,2 Masamichi Ishioka,3 Kazutoshi Kubo,4 Katsuji Suzuki,5 Akira Fujii,6 Hanako Furukori,7 Taku Nakagami,8 Norio Yasui-Furukori,1,2 Kazutaka Shimoda1 1Department of Psychiatry, Dokkyo Medical University School of Medicine, Mibu, Japan; 2Department of Neuropsychiatry, Hirosaki University Graduate School of Medicine, Hirosaki, Japan; 3Department of Psychiatry, Minato Hospital, Hachinohe, Japan; 4Department of Neuropsychiatry, Hirosaki-Aiseikai Hospital, Hirosaki, Japan; 5Department of Psychiatry, Aomori Central Hospital, Aomori, Japan; 6Department of Neuropsychiatry, Mutsu General Hospital, Mutsu, Japan; 7Department of Neuropsychiatry, Kuroishi-Akebono Hospital, Kuroishi, Japan; 8Department of Psychiatry, Nakagami Mental Clinic, Ohdate, JapanCorrespondence: Norio Yasui-FurukoriDepartment of Psychiatry, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi, 321-0293, JapanTel +81-28-287-2153Fax +81-28-286-5187Email furukori@dokkyomed.ac.jpBackground: Concern regarding the benefit/risk ratio of the long-term use of benzodiazepines (BDZs) and Z-drugs is increasing. To prevent the risk of dependence in BDZ long-term use, it is essential to understand the attitudes of patients and psychiatrists toward BDZ treatment. The aims of this investigation were to 1) obtain information on patients’ attitudes with long-term BDZ use and their referring psychiatrists’ attitudes toward BDZ treatment, including their perception of the difficulty of reducing the dose of BDZs, and 2) identify discrepancies between patients’ and psychiatrists’ perceptions.Methods: A brief questionnaire was constructed to investigate the attitudes of patients receiving BDZ treatment and their referring psychiatrists. Our sample comprised 155 patients who received BDZ treatment for more than one year and their referring eight psychiatrists. Both the patients and their psychiatrists completed our questionnaire between August 2017 and December 2017.Results: Of the patients, 13% felt that it was more difficult to reduce the dose of BDZs than their referring psychiatrists (type A discrepancy), while 25% felt that it was less difficult (type B discrepancy). In the multivariate logistic regression analysis, the female sex and both the patients’ (“psychotherapy plus BDZs was necessary” and “it was necessary to increase the dose of BDZs”) and psychiatrists’ beliefs (“short-term prescription was justified”) were associated with type A discrepancies. Type B discrepancies were associated with psychiatrists’ beliefs that the patient’s wishes justified the use of BDZs and that the cessation of treatment with BDZs would lead to the deterioration of their rapport with their patients.Conclusion: To overcome the discrepancies in the attitudes of patients and psychiatrists toward the cessation of BDZ treatment, it is necessary to promote patient-centered care involving patient psychoeducation and practice guidelines for the decision-making process. Further studies investigating the promotion of patient-centered care to reduce BDZ use are needed.Keywords: dependence, benzodiazepine receptor agonist, anxiolytics, hypnotics, belief

Keita Suzuki,1 Hiromasa Tsujiguchi,1– 3 Sakae Miyagi,3,4 Thao Thi Thu Nguyen,2 Akinori Hara,1– 3 Haruki Nakamura,2 Yukari Shimizu,5 Koichiro Hayashi,1 Yohei Yamada,1 Phat Minh Nguyen,2 Yuichi Tao,2 Takayuki Kannon,3,6 Atsushi Tajima,3,6 Hiroyuki Nakamura1– 3 1Department of Public Health, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Ishikawa 920-8640, Japan; 2Department of Environmental and Preventive Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8640, Japan; 3Kanazawa University Advanced Preventive Medical Sciences Research Center, Kanazawa, Ishikawa 920-8640, Japan; 4Innovative Clinical Research Center, Kanazawa University, Kanazawa, Ishikawa 920-8640, Japan; 5Department of Nursing, Faculty of Health Sciences, Komatsu University, Komatsu, Ishikawa 923-0961, Japan; 6Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Ishikawa 920-8640, JapanCorrespondence: Keita SuzukiDepartment of Public Health, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, 13-1, Takara-Machi, Kanazawa, Ishikawa 920-8640, JapanTel +81-76-265-2218Fax +81-76-234-4233Email keitasuzuk@stu.kanazawa-u.ac.jpPurpose: Although the explanation for inconsistencies in the reported association between serum 25-hydroxyvitamin D [25(OH)D] levels and chronic pain (CP) has not yet been determined, understanding this discrepancy is necessary for the development of vitamin D supplementation as an effective treatment for CP. The aim of this cross-sectional study was to examine the relationship between 25(OH)D concentrations and CP according to drinking habits in Japanese subjects.Patients and Methods: We distributed invitation letters to 2314 individuals older than 40 years in Shika town, a rural area in Japan, and 724 subjects (386 females; mean age: 63.9 ± 10.4 years) were recruited. CP was defined as persistent pain lasting at least 3 months in any part of the body. Serum concentrations of 25(OH)D, a biomarker of the vitamin D status, were measured using a radioimmunoassay. A serum 25(OH)D level < 20 ng/mL was defined as serum 25(OH)D deficiency. Drinking habits were assessed using a self-administered questionnaire. There were three choices, “rarely drink”, “sometimes” and “everyday”. Respondents who answered “rarely drink” were labelled as non-drinkers and the others as drinkers.Results: The prevalence of CP was 40.6%. A significant interaction between CP and drinking habits on 25(OH)D concentrations was observed (p = 0.098). A one-way analysis of covariance was performed to compare 25(OH)D concentrations between the subjects with and without CP in each drinking group, and the serum 25(OH)D levels of subjects with CP were significantly lower than those without CP among drinkers (p = 0.007). A logistic regression analysis revealed a correlation between serum 25(OH)D deficiency and CP in drinkers after adjustments for several confounding factors (odds ratio: 0.499; 95% confidence interval: 0.268 − 0.927; p = 0.028).Conclusion: The present results suggest that low serum 25(OH)D concentrations are associated with the development of CP in drinkers.Keywords: pain, vitamin D, alcohol, cross-sectional analysis, epidemiology

The current understanding of light hypernuclei, which are sub-atomic nuclei with strangeness, is being challenged and studied in detail by several European research groups and collaborations. In recent years, studies of hypernuclei using high-energy heavy ion beams have reported unexpected results on the three-body hypernuclear state 3ΛH, named the hypertriton. For some time, reports of a shorter lifetime and larger binding energy than what was previously accepted have created a puzzling situation for its theoretical description; this is known as the "hypertriton puzzle". With the inclusion of the most recent experimental measurements, the current status of the hypertriton puzzle is evolving. Additionally, the possible neutral bound state of a Λ hyperon with two neutrons, nnΛ, has raised questions about our understanding of the formation of light hypernuclei either in bound or resonance states. These results have initiated several ongoing experimental programs all over the world to study these three-body hypernuclear states precisely. We are studying these light hypernuclear states by employing heavy ion beams at 2AGeV on a fixed carbon target with the WASA detector system and the Fragment Separator (FRS) at GSI. The WASA-FRS experimental campaign was performed during the first quarter of 2022, and this paper presents a short overview of the campaign and how it seeks to tackle the hypertriton and nnΛ puzzles. Data analysis is ongoing, and several preliminary results will be reported.

Kazuyoshi Kawakami,1 Takeru Wakatsuki,2 Azusa Soejima,1 Kazuo Kobayashi,1 Takashi Yokokawa,1 Takeshi Aoyama,1 Kenichi Suzuki,1 Mitsukuni Suenaga,2 Kensei Yamaguchi,2 Ayaka Inoue,3 Yoshiaki Machida,3 Toshihiro Hama1 1Department of Pharmacy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-Ku, Tokyo 135-8550, Japan; 2Department of Gastroenterological Chemotherapy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-Ku, Tokyo 135-8550, Japan; 3Section for Practical Education, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Shinagawa-Ku, Tokyo 142-8501, JapanCorrespondence: Kazuyoshi KawakamiThe Japanese Foundation for Cancer Research, Cancer Institute Hospital, Depatment of Pharmacy, 3-8-31 Ariake Koto-ku, Tokyo 135-8550, JapanEmail kazu.kawakami@jfcr.or.jpIntroduction: Regorafenib is an oral multikinase inhibitor for the treatment of metastatic colorectal cancer (mCRC). The clinical factors that may affect adherence to regorafenib remain unclear. The aim of this study was to evaluate adherence to regorafenib with mCRC and to identify factors that might affect adherence to regorafenib.Methods: A total of 108 consecutively enrolled Japanese patients with mCRC received regorafenib. Adherence was measured by pharmacists using pill counts and a self-reported treatment diary for patients at a pharmaceutical outpatient clinic. The median relative dose intensities of regorafenib and the factors adversely affecting adherence were retrospectively surveyed. Logistic regression analysis was then performed using patient socio-demographic factors and clinical factors.Results: A total of 96 patients were included in the analysis. The median adherence rate was 61.7% in the first cycle. The median relative dose intensity was 57.1%. The most common reason for non-adherence was a hand-foot-skin reaction (35.6%). On multivariate analysis, increased non-adherence to regorafenib was significantly associated with sex (female) [odds ratio (OR) = 4.36; 95% confidence interval (CI): 1.43–13.22, p = 0.01].Discussion: Hand-foot-skin reactions and female sex were associated with lower adherence to regorafenib. Since these factors could be associated with lower adherence to regorafenib, it would be useful to consider these factors when assessing adherence.Keywords: adherence, regorafenib, colorectal cancer, hand-foot-skin reactions

Masashi Sakayori,1 Jiro Terada,1 Mitsuhiro Abe,1 Yasutaka Hirasawa,1 Kenichi Suzuki,1 Keiichiro Yoshioka,1 Kenji Tsushima,2 Koichiro Tatsumi11Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; 2Department of Pulmonary Medicine, International University of Health and Welfare, School of Medicine, Chiba 286-8686, JapanPurpose: Although pirfenidone (PFD) is a key drug for the treatment of idiopathic pulmonary fibrosis (IPF), differences in tolerability between elderly and young patients remain unclear. This study aimed to investigate age-related differences in adverse drug reactions to PFD and to evaluate whether patient age influences the safety and tolerability of PFD in clinical practice.Patients and method: One hundred fifty-four patients with IPF were treated with PFD in our institution between May 2009 and April 2017; these patients were classified into 2 groups on the basis of age: ≥75 years of age (elderly patients) and

Mitsugi Shimoda, Tsunehiko Maruyama, Kiyotaka Nishida, Kazuomi Suzuki, Tomoya Tago, Jiro Shimazaki, Shuji SuzukiDepartment of Gastroenterological Surgery, Tokyo Medical University, Ibaraki Medical Center, Ami, Ibaraki, JapanBackground: Laparoscopic appendectomy (LA) has been increasingly adopted for its advantages over the open appendectomy, but there are possibilities of conversion from laparoscopic to open appendectomy (CA) if the patients had complicated appendicitis concurrently, or when the extent of inflammation prohibits successful procedure. In this retrospective study, we aimed to clarify the preoperative predictors for CA.Patients and methods: From January 2010 to April 2016, medical records of 93 consecutive patients who underwent LA for suspected appendicitis were reviewed retrospectively. Factors evaluated were age, gender, body mass index, C-reactive protein (CRP), white cell count, albumin, Neutrophil count, lymphocyte count, Neutrophil/lymphocyte ratio, preoperative CT imaging (abscess formation: yes/no, appendicolith: yes/no), operative factors (time to operation, amount of bleeding), length of hospital stay, period until oral intake after surgery, and period from initial symptoms to surgery.Results: CA occurred in nine patients (9.7%). The reason for conversion was severe dense adhesion in two cases, inadequate exposure of appendix in two cases, uncompleted appendectomy in two cases, perforated appendicitis in one case, gangrenous appendicitis in one case, and abscess formation in one case. Based on 93 patients evaluated by preoperative CT scan, significant factors in the final multivariate analysis associated with CA was CRP [odds ratio=1.13, 95% CI:1.00–1.28, p=0.04].Conclusion: Identifying the potential factors for conversion preoperatively may assist the surgeons in making decisions concerning the management of patients with appendicitis and in the judicious use of LA.Keywords: laparoscopic, conversion, appendectomy, C-reactive protein

Yosuke Kameoka,1 Fukuko Kishi,1 Minako Koura,2 Yoshio Yamakawa,1 Rora Nagasawa,1 Fuyu Ito,3 Junichiro Matsuda,2 Osamu Suzuki,2 Toshinori Nakayama,4 Kazuo Suzuki1,3–5 1Department of Research and Development, A-CLIP Institute, Ltd., Chiba, Japan; 2Laboratory of Animal Models for Human Diseases, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan; 3Asia International Institute of Infectious Disease Control, Teikyo University, Tokyo, Japan; 4Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan; 5Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan Background: Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis is a pauci-immune disease with the inflammation of the small blood vessels. The efficacies of antibody drugs for induction therapies of vasculitis vary among cases. Here, we developed a novel clone of a single chain Fv region (ScFv) with vasculitis-specific therapeutic potential.Materials and methods: The clone, termed VasSF, was selected from our Escherichia coli expression library of recombinant human ScFv based on the therapeutic efficacy in an SCG/Kj mouse model of MPO-ANCA-associated vasculitis (MAAV), such as improvement of the urinary score and decreased crescent formation in glomeruli, granulomatous in lung, MPO-ANCA biomarkers, the anti-moesin antibody, and some cytokine levels.Results: We identified vasculitis-associated apolipoprotein A-II (VAP2) as a target molecule of the clone and confirmed the independently-established VAP2 antibodies were also therapeutic in SCG/Kj mice. In MAAV, MPO-ANCA and cytokines stimulate neutrophils by facilitating heterodimer formation of VAP2 with apolipoprotein A-I in HDL. Conclusion: VasSF would constitute a novel antibody drug for vasculitis by suppressing the heterodimer formation of the apolipoproteins. Keywords: VasSF, ANCA antibody drug, apolipoprotein, HDL, myeloperoxidase, MPO, SCG/Kj, vasculitis

JLab E12-19-002 Experiment is planned to measure the Λ-binding energies of 3ΛH [Jπ = 1/2+ or 3/2+(T = 0)] and 4ΛH (1+) at JLab Hall C. The expected accuracy for the binding-energy measurement is |ΔBtotal Λ | ≃ 70 keV. The accurate spectroscopy for these light hypernuclei would shed light on the puzzle of the small binding energy and short lifetime of 3ΛH, and the chargesymmetry breaking in the ΛN interaction. We aim to perform the experiment in 2025.

Missing-mass spectroscopy with the 3H(e, e′K+) reaction was carried out at Jefferson Lab’s (JLab) Hall A in Oct–Nov, 2018. The differential cross section for the 3H(γ∗, K+)Λnn was deduced at ω = Ee − Ee′ = 2.102 GeV and at the forward K+-scattering angle (0° ≤ θγ∗K ≤ 5°) in the laboratory frame. Given typical predicted energies and decay widths, which are (BΛ, Γ) = (−0.25, 0.8) and (−0.55, 4.7) MeV, the cross sections were found to be 11.2 ± 4.8(stat.)+4.1−2.1(sys.) and 18.1 ± 6.8(stat.)+4.2−2.9(sys.) nb/sr, respectively. The obtained result would impose a constraint for interaction models particularly between Λ and neutron by comparing to theoretical calculations.

We performed an experiment using tritium and hydrogen cryogenic gas targets at Thomas Jefferson National Accelerator Facility (JLab) in 2018 (E12-17-003)[1, 2]. In this article, we discuss the Λ/Σ0 hyperon electroproduction from hydrogen target. Elementary Λ/Σ0 hyperon production processes are important not only for an absolute mass scale calibration in our experiment, but also for the study of the electroproduction mechanisms themselves. In this article, we reported the results of the differential cross section for the p(e, e’K+)Λ/Σ0 reaction at Q2 ∼ 0.5 (GeV/c)2.

A new hyperon-proton scattering experiment, dubbed J-PARC E40, was performed to measure differential cross sections of the Σ+p, Σ−p elastic scatterings and the Σ−p → Λn scattering by identifying a lot of Σ particles in the momentum ranging from 0.4 to 0.8 GeV/c produced by the π±p → K+Σ± reactions. We successfully measured the differential cross sections of these three channels with a drastically improved accuracy with a fine angular step. These new data will become important experimental constraints to improve the theories of the two-body baryon-baryon interactions. Following this success, we proposed a new experiment to measure the differential cross sections and spin observables by using a highly polarized Λ beam for providing quantitative information on the ΛN interaction. The results of three Σp channels and future prospects of the Λp scattering experiment are described.

Yukihiko Suzuki, Kobu Adachi, Yoshihiro Jinnai, Kaori Suzuki, Mitsuru Nakazawa Department of Ophthalmology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan Abstract: We developed intraocular lens (IOL) fixation procedure that only uses one suture during Zinn’s zonule dialysis portion of the combined surgery for IOL intracapsular fixation and unilateral loop suture for preserving the lens capsule. We treated 15 eyes in 15 patients which were confirmed to have almost 180° zonular dialysis during cataract surgery. After removing the lens, a scleral flap was created on the dialysis side. A straight needle for suturing was then inserted into the anterior chamber from the opposite side of the dialysis. The needle was used to attach the equatorial segment of the capsule on the dialysis side from the inside to the outside and then pull the suture thread under the scleral flap. After the thread was bound to a preceding loop of IOL, the IOL was inserted into the bag. Our procedure was found to be simple and less invasive, as our technique required no vitrectomy to be performed. Keywords: intraocular lens, zonular dialysis, IOL scleral suturing, cataract surgery

Kazuhiro Hayashi,1–3 Masato Kako,3 Kentaro Suzuki,3 Yui Takagi,3 Chiaki Terai,3 Shotaro Yasuda,3 Izumi Kadono,3 Taisuke Seki,4 Hideki Hiraiwa,4 Takahiro Ushida,1 Yoshihiro Nishida3,4 1Multidisciplinary Pain Center, Aichi Medical University, Nagakute, Japan; 2Department of Rehabilitation, Aichi Medical University Hospital, Nagakute, Japan; 3Department of Rehabilitation, Nagoya University Hospital, Nagoya, Japan; 4Department of Orthopaedic Surgery, Nagoya University Graduate School and School of Medicine, Nagoya, Japan Purpose: Patients who undergo total knee arthroplasty (TKA) or total hip arthroplasty (THA) often develop postoperative pain. Exercise approaches are recommended postoperatively; however, the impact of excessive variation in physical activity is unclear. The purpose of the present preliminary study was to investigate the impact of excessive variation in physical activity using the accelerometer in the early period after TKA or THA. Patients and methods: Seventy-two patients were enrolled in the study. Forty patients underwent initial TKA, and 32 initial THA. Physical activity was measured for 8 days from postoperative day 3 to 10. Patients with substantial correlation between physical activity and postoperative day were classified as the “good-pacing” group. Patients with no correlation between them were classified as the “poor-pacing” group. They were also evaluated using a pain visual analog scale (VAS), pain catastrophizing scale, and hospital anxiety and depression scale. Results: The average age was 68 years, and 59 patients (82%) were women. The average maximum number of steps per day was 2,181. There were 45 patients with good pacing and 27 with poor pacing. The poor-pacing group showed significantly lower maximum number of steps per day, higher postoperative average VAS score, higher postoperative worst VAS score, and longer duration of postoperative hospital stay than the good-pacing group. Conclusion: Patients with excessive variation in physical activity showed severe postoperative pain and prolonged postoperative hospital stay. The postoperative variation in physical activity could be an outcome for improvement in patients after lower-limb arthroplasty. Keywords: total joint arthroplasty, postoperative pain, rehabilitation, pacing, accelerometer

Mitsuhiro Abe,1 Kenji Tsushima,1,2 Masashi Sakayori,1 Kenichi Suzuki,1 Jun Ikari,1 Jiro Terada,1 Koichiro Tatsumi1 1Department of Respirology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba city, Chiba 260-8670, Japan; 2Department of Pulmonary Medicine, International University of Health and Welfare, School of Medicine, Narita city, Chiba 286-8686, Japan Introduction: The INPULSIS-ON trial demonstrated that nintedanib reduced decline in forced vital capacity (FVC) and low pulmonary function (%FVC < 50%) of patients with idiopathic pulmonary fibrosis (IPF). However, there is no sufficient evidence in real world.Objectives: Reveal the utility and adverse events of nintedanib for severe IPF patients.Methods: This was a single-center retrospective study. Patients who met the eligibility criteria of the INPULSIS trial (%FVC ≥ 50%; %DLCO [diffusing capacity of the lung carbon monoxide % predicted] ≥ 30%) were classified as Mild to Moderate Group (n = 34); patients who did not meet the criteria were classified as Severe Group (n=17).Results: The body mass index (24.7 ± 3.4 vs 22.4 ± 3.6 kg/m2; P = 0.021) were significantly low in Severe Group. Main adverse events (diarrhea, nausea, liver disorder, and acute exacerbation) tended to be more in Severe Group than in Mild to Moderate Group; however, the difference was not significant (P = 0.76, 0.14, 0.18, and 0.67, respectively). The continuation rates over 12 months tended to be higher in Mild to Moderate Group than in Severe Group (77% vs 44%; P = 0.027). Log-rank test revealed that the prognosis was significantly better in Mild to Moderate Group than in Severe Group (P = 0.014). In the Severe Group, patients who were able to continue nintedanib for more than 3 months had significantly better prognosis compared to those who could not (P = 0.007).Conclusion: The benefit from nintedanib was reduced in patients in Severe Group when compared to those in Mild to Moderate Group; however, the prognosis is expected to improve with control of side effects and long-term administration. It is more important to control the side effects in Severe Group. Keywords: idiopathic pulmonary fibrosis, nintedanib, triple tyrosine kinase inhibitor, INPULSIS trials, forced vital capacity

Takao Arai,1 Shoichi Ohta,1 Masaki Onishi,2 Miyu Taniguchi,1 Junya Tsurukiri,1 Kenichiro Kumasaka,1 Katsuhiro Nagata,1 Kensuke Suzuki,3 Ken Harigae,4 Tetsuo Yukioka1 1Department of Emergency and Critical Care Medicine, Trauma and Emergency Center, Hachioji Medical Center, Tokyo Medical University, Tokyo, Japan; 2National Institute of Advanced Industrial Science and Technology, Tokyo, Japan; 3Faculty of Medical Science, Nippon Sport Science University, Yokohama, Kanagawa, Japan; 4Emergency Department, Hino Municipal Hospital, Hino, Tokyo, Japan Purpose: It is difficult for emergency physicians to plan and execute a disaster medical response drill while conducting their daily work activities. Readily available drill preparation manuals are therefore essential, alongside assessment methods to ensure quality. Here, we propose email text analysis as a manual assessment method, and investigate its validity. Methods: The preparation status of two similar large-scale disaster medical response drills were compared. All email texts exchanged during the preparation stage were analyzed, and frequently appearing words (quality element) and word counts (quantity element) were compared between Drill 1, which was organized without a manual, and Drill 2, organized with a manual. Results: Word frequency analysis revealed that the key components of the manual (visualization of necessary work, preparation of documents in a certain format, and clarification of aims of the drill) contributed to the effectiveness of the preparation process for Drill 2. Furthermore, work volume during the preparation for Drill 2 was decreased by 41.9% from that during the preparation for Drill 1. Conclusion: Preparation of a high-quality manual is crucial so that emergency physicians can plan and execute a disaster medical response drill. Email text analysis can serve as an objective method assessing the quality of manuals. Keywords: disaster medicine, textual analysis, database, quality assessment

Introduction: Patients with traumatic intracranial hemorrhage (ICH) or skull fracture are typically admitted to the Department of Neurosurgery for fear of delayed neurological deterioration. Neurosurgeons, therefore, must be careful not to overlook a spinal fracture in these patients. In this study, we investigated the occurrence and risk factor of spinal fracture in patients with traumatic ICH or skull fracture. Patients and methods: We retrospectively analyzed the hospital records of 134 patients admitted to the Department of Neurosurgery at Kagawa Rosai Hospital for traumatic ICH or skull fracture. The etiology of trauma, level of consciousness, presence or absence of ICH, skull fracture, craniotomy and spinal surgery were investigated. Furthermore, in cases of spinal fracture, its type, neurological symptoms, treatment were investigated. Results: In an analysis of 134 patients, Ground level fall and traffic accident were the most frequent etiologies of trauma (47.0% and 23.9% respectively). Glasgow coma scale on admission was 15-13 for 106 patients (79.1%). Spinal fracture was identified in 10 of 134 patients (7.5%). Two patients had cervical, 8 had thoracolumbar fractures. In the analysis of risk factors, an accidental fall and skull fracture was observed significantly more in the spinal fracture cases. Conclusion: The majority of traumatic ICH or skull fracture cases treated in the Department of Neurosurgery were caused by minor head impacts. When treating these patients, it is necessary to investigate not only the cervical, but also the thoracolumbar spine, especially when the cause of injury is an accidental fall and a skull fracture is identified.

Abe M, Tsushima K, Sakayori M, et al. Drug Des Devel Ther. 2018;12:3369–3375.On page 3372, last paragraph of “Results” section should read from “In Severe Group, patients who were able to continue nintedanib for more than 3 months (n = 4) exhibited significantly better prognosis compared to those who could not (n = 13) (P = 0.007) (Figure 6).” to “In Severe Group, patients who were able to continue nintedanib for more than 3 months (n = 13) exhibited significantly better prognosis compared to those who could not (n = 4) (P = 0.007) (Figure 6).”Read the orginal article

Yasuo Sekine, Ryoko Yanagibori, Kiminori Suzuki, Sonomi Sugiyama, Haruko Yamaji, Michiko Ishibashi, Takehiko Fujisawa Chiba Foundation for Health Promotion and Disease Prevention, Chiba, Japan Background and objective: Patients with chronic obstructive pulmonary disease (COPD) are at risk for lung cancer; the diseases have common etiologies, including cigarette smoking. We aimed to clarify the effectiveness of COPD detection using a regional mass-screening program for lung cancer. Materials and methods: A total of 7,067 residents of Togane, Chiba, Japan received lung cancer screening between May and July, 2011. We defined four groups of possible COPD candidates: group A (n=358), positive smoking history, positive chronic respiratory symptoms; group B (n=766), positive smoking history, positive lifestyle-related disease; group C (n=75), passive smoking history, positive chronic respiratory symptoms; and group D (n=301), passive smoking history, positive lifestyle-related disease. Candidates underwent on-site pulmonary function testing (PFT). Results: The criteria for COPD candidates were fulfilled in 1,686 of 7,067 individuals (23.9%); 1,500 participants underwent PFT (89%), and 171 (11.4%) were diagnosed with COPD. The overall COPD detection rate was 2.4%. The frequency of COPD was significantly higher in groups A and B than in groups C and D (P=0.048); however, the distribution of COPD grades was similar among the groups (P=0.372). Multiple logistic regression analysis identified male sex, age 60 years or greater, and positive smoking history as risk factors for COPD. Conclusion: COPD screening using a community-based lung cancer-screening program may be effective for disease detection. Individuals who are 60 years of age or older with a positive smoking history should undergo PFT to detect COPD. Keywords: chronic obstructive pulmonary disease, lung neoplasms, mass screening, respiratory function tests

Toshimi Chiba, Kazunari Yamamoto, Shoko Sato, Kazuyuki Suzuki Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Iwate, Japan Abstract: Irritable bowel syndrome (IBS) is a functional disease with persisting gastrointestinal symptoms that has been classified into four subtypes. Serotonin (5-hydroxytryptamine [5-HT]) plays important physiological roles in the contraction and relaxation of smooth muscle. Intraluminal distension of the intestine is known to stimulate the release of endogenous 5-HT from enterochromaffin cells, activating 5-HT3 receptors located on primary afferent neurons and leading to increases in intestinal secretions and peristaltic activity. Ramosetron, a potent and selective 5-HT3-receptor antagonist, has been in development for use in patients suffering from diarrhea-predominant IBS. In a double-blind, placebo-controlled, parallel-group study of 418 patients with diarrhea-predominant IBS-D, once-daily 5 µg and 10 µg doses of ramosetron increased the monthly responder rates of IBS symptoms compared to placebo. In a 12-week randomized controlled trial of 539 patients, a positive response to treatment was reported by 47% of a once-daily 5 µg dose of ramosetron-treated individuals compared to 27% of patients receiving placebo (P

Hiromi Kimura, Akemi Osaki, Rui Kawashima, Takeshi Inoue, Shin Nakagawa, Katsuji Suzuki, Satoshi Asakura, Teruaki Tanaka, Yuji Kitaichi, Takuya Masui, Nobuki Kitagawa, Yuki Kako, Tomohiro Abekawa, Ichiro Kusumi, Hiroyoshi Yamanaka, Kenzo Denda, Tsukasa KoyamaDepartment of Psychiatry, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, JapanBackground: The bipolar-unipolar distinction in patients with a major depressive episode is the most important issue related to the diagnosis and treatment of mood disorders, but remains unresolved. This study was undertaken to compare bipolar and unipolar depression on Rorschach testing using the Comprehensive System with reference to healthy Japanese controls.Methods: Patients with bipolar or unipolar depression who had undergone the Rorschach test for routine clinical purposes were followed up naturalistically for a long period. Based on diagnostic confirmation after long-term follow-up, scores on this test for patients with bipolar and unipolar depression were compared with those published elsewhere for healthy Japanese controls.Results: The bipolar depression group showed significantly higher scores or positive findings in five variables of the Rorschach test, ie, WSum6, DR2 > 0, (CF + C) > FC + 2, PureC > 1, and Populars > 7, as assessed using the Comprehensive System, than did the unipolar depression group and healthy controls. These scores did not differ between the unipolar depression and control groups.Conclusion: The results of this study show thought disorder or cognitive slippage and marked laxness in modulating emotion in bipolar depression, indicating the psychopathological characteristics of bipolar disorder.Keywords: bipolar depression, bipolar disorder, Rorschach test, thought disorder, unipolar depression

Total cross section for the double neutral pion photoproduction off the proton is presented in the incident photon energy range of 0.58 to 1.15 GeV. The data were accumulated in the years 2009–2010, recorded by a 4π EM calorimeter at ELPH, named FOREST. The number of recorded events obtained during this period is 1.6×109 for a hydrogen target. Two neutral pions are reconstructed via detecting their decay products, four gammas (2π0 → 4γ). Compared to the previous results obtained by other groups, our data are in good agreement with theirs within error bars.